Abstract

Background

The hTERT (human telomerase reverse transcriptase) gene contains five variable number tandem
repeats (VNTR) and previous studies have described polymorphisms for hTERT-VNTR2-2nd. We investigated how allelic variation in hTERT-VNTR2-2nd may affect susceptibility to prostate cancer.

Methods

A case-control study was performed using DNA from 421 cancer-free male controls and
329 patients with prostate cancer. In addition, to determine whether the VNTR polymorphisms
have a functional consequence, we examined the transcriptional levels of a reporter
gene linked to these VNTRs and driven by the hTERT promoter in cell lines.

Results

Three new rare alleles were detected from this study, two of which were identified
only in cancer subjects. A statistically significant association between rare hTERT-VNTR2-2nd alleles and risk of prostate cancer was observed [OR, 5.17; 95% confidence interval
(CI), 1.09-24.43; P = 0.021]. Furthermore, the results indicated that these VNTRs inserted in the enhancer
region could influence the expression of hTERT in prostate cancer cell lines.

Conclusions

This is the first study to report that rare hTERT VNTRs are associated with prostate cancer predisposition and that the VNTRs can induce
enhanced levels of hTERT promoter activity in prostate cancer cell lines. Thus, the hTERT-VNTR2-2nd locus may function as a modifier of prostate cancer risk by affecting gene expression.